The present disclosure relates to implantable cardiac pulse generators (IPGs) generally, and more particularly to implantable cardioverters defibrillators (ICDs) and triple-chamber pacing devices configured to deliver cardiac resynchronization therapy (CRT).
Cardiac conduction defects and various co-morbidities of heart failure can confound the natural cardiac depolarization sequence so that upper and lower chambers fail to electrically conduct and mechanically contract during normal sinus rhythm (NSR) and/or without ventricular synchrony. In certain heart failure patients, the heart may become dilated, and the conduction and depolarization sequences of the heart chambers may, for example, exhibit inter- and/or intra-atrial conduction defects (IACD), left bundle branch block (LBBB), right bundle branch block (RBBB), and inter-ventricular conduction defects (IVCD) and the like. In patients suffering from each or a combination of such conduction defects, a lack of synchrony and/or complementary blood flow among the chambers can diminish cardiac output and impair perfusion of the organs of tissues of the patient. In addition, spontaneous depolarizations originating within the right atrium, left atrium (RA, LA), the right ventricle (RV), and/or the left ventricle (LV) can arise from diverse locations (e.g., at one or more ectopic foci) thus disturbing the natural activation sequence. Further, significant conduction disturbances between the RA and LA can result in atrial flutter or fibrillation (e.g., which can significantly impair LV filling due to the arrthymia within the LA).
It has been found that various conduction disturbances involving both bradycardia and tachycardia conditions could be overcome by applying pacing pulses at multiple electrode sites positioned in or about a single or multiple chambers of a heart in synchrony with a depolarization that is sensed at one of multiple electrode sites. It is known that cardiac output can be significantly improved when left and right chamber synchrony is restored.
Cardiac resynchronization therapy (CRT) is one of the most successful heart failure (HF) therapies to emerge in the last 25 years and is applicable to 25-30% of patients with symptomatic HF, especially those with abnormal impulse conduction through the ventricles, such as left bundle branch block (LBBB). Since initial approval of the therapy over 10 years ago, there have been hundreds of thousands of implants worldwide. Although the effects of CRT on the population level are impressive, benefits at the individual level vary considerably. Depending on the definition, the response to CRT is positive in 50-70% of patients, leaving 30-50% without significant effect. Such lack of response is especially not desirable, since CRT requires the virtually irreversible implantation of a costly device and pacing electrodes during an invasive procedure.
Effectiveness of CRT can be improved by optimal programming of the device, especially with regard to the time delay (AV-interval) between electrical stimulation of the right atrium (RA) and the ventricles and the time delay (VV-interval) between stimulation of the Right ventricle (RV) and the left ventricle (LV). Such CRT optimization increases acute hemodynamic benefits of CRT by 20-30% and improves short-term clinical response. In half of CRT clinical non-responders it is believed that symptoms could be improved by careful AV- and VV-optimization. In regular clinical practice also AV- and VV-intervals are used in the “out-of-the-box” default settings.
Echocardiographic techniques can be used to optimize AV- and VV-delays, but such optimization procedures are relatively complicated procedures and the echocardiographic measurements are notoriously inaccurate. A further serious limitation of echocardiographic optimization is that it is performed in the recumbent position in full rest, while optimization is likely more required under more conditions of higher physical activity.
The group of Prof. Prinzen has collected evidence in animal experiments and CRT patients that the QRS complex in the vectorcardiogram (VCG), measured at the body surface, provides an accurate description of the degree of resynchronization during the various AV- and VV-intervals. The results of this study are presented in “Vectorcardiography as a tool for easy optimization of cardiac resynchronization in canine LBBB hearts”; Van Deursen, et al, Circ. Arrhythm. Electrophysiol, 2012; 5:544-522, incorporated herein by reference in its entirety. This study also showed that accuracy of QRS vector determination is considerably higher than that of hemodynamic measurements.
Subsequently, in a group of 11 patients it was observed (see FIG. 1) that the best hemodynamic response (“VTILVOT”) and the most physiological contraction pattern (minimal value of SPS+SRS) occur at AV- and VV-intervals where the three-dimensional area of the QRS-complex on the VCG loop (QRSVarea) is minimal. This minimal QRS-area, which can be determined using surface ECG measurements, provides an easy and accurate index for initial programming of optimal AV- and VV-intervals.
FIG. 1 illustrates the use of surface VCG for optimization of CRT, showing data from a representative CRT patient. The AV-delay at which QRSV area was minimal coincided with the AV-delay where a minimal value was found for the sum of septal systolic pre-stretch (SPS) and rebound stretch (SRS; indicating the least abnormal septal contraction) as well as the highest value of VTILVOT (˜stroke volume). In 11 patients difference between actual maximal increase in VTILVOT relative to LBBB and VCG-predicted increase was small (−0.4%; IR−1.6 to 0% and −0.5%; IR−1.3 to −0.2% respectively). Surface VCGs thus provide a useful tool in conjunction with both initial implant and later follow-up visits for adjustment of stimulation parameters.
In this prior study, The Inventors also found that the measured surface QRS vector amplitude also could be used to optimize A-V and V-V delay. In this case, the combination of A-V and V-V intervals that produced a surface QRS vector amplitude halfway between that seen during LV pacing at short A-V intervals and that seen during un-paced LBBB rhythm corresponded to minimal QRSV area and to optimal hemodynamic performance.
Such optimization can be performed briefly after implantation of the CRT device. However, as the patient's disease state evolves, for example, due to an acute heart failure decompensation event or because of deleterious remodeling that occurs in the progression of heart failure or otherwise during the course of heart failure treatment and therapy, the optimal A-V and/or V-V timing may change between physician visits as well and thus would benefit from a closed loop method and apparatus for adapting to same. A similar condition may arise during physical exercise, when conduction properties of the heart may change due to activation of the sympathetic and parasympathetic nervous system.